DESCRIPTION: Almost a million people are ill from malaria each day while severe malaria disease claims the lives of 600,000 people each year. A rugged, portable sensitive and accurate method to diagnose malaria without blood sampling and using the reagents would be ideal and addresses the critical problem of malaria diagnosis in field or in asymptomatic cases. The MalariSense technology is able to make a diagnosis through the skin within seconds without using reagents or a needle to obtain blood. The device works by shining a short safe laser pulse that penetrates the skin to small blood vessels. The malaria parasite has a crystal inside of itsel that is able to absorb the laser energy to make a small vapor nanobubble that expands and collapses. The collapsing vapor nanobubble generates a pressure wave that is able to be detected by an ultrasound detector. Uninfected red blood cells are not affected by the laser and do not make a vapor bubble. The proof of MalariSense concept was demonstrated in animals and humans by shining a laser on the ear and detecting the sound pings. In this project, the discovered mechanism will be translated into a field, easy-to-use diagnostic device to non- invasively detect both symptomatic and asymptomatic malaria infections in seconds, and to screen > 200,000 people per year with a single device with a diagnosis cost below 0.1$. This will be achieved through several connected activities: (1) Determine the methodology and specifications for the MalariSense technology; (2) Develop and prototype the MalariSense technology for field use; (3) Evaluate the MalariSense technology in endemic area, determine its performance and applications, and develop the platform for a global screening of malaria. The applications for analyzing mosquitoes, blood samples and small animals will also be developed and tested the ability to make the sensitive diagnosis of malaria through the skin opens up a whole new dimension to malaria diagnosis. The impact and applications are many. The ability to diagnose and treat asymptomatic people living in malaria areas will help greatly the strategies to eliminate malaria from regions. Another dimension of the device is the ability to enable the immediate global access and analysis of the raw data for the remote monitoring of malaria infection. The developed software, protocol and device will act as a platform for the future implementation of the global malaria diagnostic system to radically improve the malaria control and elimination in multiple settings. Just 1000 units will annually screen 200 million people to cover all current disease cases.